Context The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor ␣ (TNF-␣). Little is known about the reactivation of latent viral infections during treatment with TNF-␣ inhibitors. Objective To investigate whether TNF-␣ inhibitors together as a class, or separately as either monoclonal anti-TNF-␣ antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis. Design, Setting, and Patients Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up. Main Outcome Measures Hazard ratio (HR) of herpes zoster episodes following anti-TNF-␣ treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-␣ inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-␣ inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs. Results Among 5040 patients receiving TNF-␣ inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti-TNF-␣ antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti-TNF-␣ treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class. Conclusion Treatment with monoclonal anti-TNF-␣ antibodies may be associated with increased risk of herpes zoster, but this requires further study.

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IntroductionThe aim of this study was to evaluate the safety and efficacy of rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in routine care, and to monitor changes in daily practice since the introduction of RTX therapy.MethodsThis was a multicentre, prospective, non-interventional study conducted under routine practice conditions in Germany. Efficacy was evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse drug reactions (ADRs). Physician and patient global efficacy and tolerability assessments were also evaluated.ResultsOverall, 2,484 patients (76.7% female, mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment (22.7% monotherapy). The total observation period was approximately six-years (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and HAQ-DI that were sustained over multiple courses. DAS28 improvements positively correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and tolerability were rated good/very good by the majority of physicians and patients. Mean treatment intervals were 10.5 and 6.8 months for the first and last 400 enrolled patients, respectively. Infections were the most frequently reported ADRs (9.1%; 11.39/100 patient-years); approximately 1% of patients per course discontinued therapy due to ADRs.ConclusionsProlonged RTX treatment in routine care is associated with good efficacy and tolerability, as measured by conventional parameters and by physicians’ and patients’ global assessments. Rheumatoid factor status served as a distinct and quantitative biomarker of RTX responsiveness. With growing experience, physicians repeated treatments earlier in patients with less severe disease activity.

The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9–3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.

Tocilizumab administered in a real-life setting showed clinically meaningful improvements and a safety profile that was consistent with data reported from pre-approval Phase III studies.

Tocilizumab (TCZ) and tumour necrosis factor inhibitors (TNFi) are recommended for the treatment of rheumatoid arthritis (RA) in patients with inadequate response (IR) to prior disease-modifying antirheumatic drugs (DMARDs). This retrospective analysis assessed the efficacy of TCZ and TNFi, alone or in combination with DMARDs, in 1603 patients with IR to previous treatment with either DMARDs (DMARD-IR) and/or TNFi (TNFi-IR), initiating treatment with TCZ or a TNFi, managed in routine clinical practice. Patients were grouped according to treatment history and treatment initiated: DMARD-IR patients initiating treatment with TCZ + DMARD (DMARD-IR TCZ) or TNFi + DMARD (DMARD-IR TNFi), DMARD-IR and/or TNFi-IR patients initiating treatment with TCZ monotherapy (TCZ mono) or TNFi monotherapy (TNFi mono), and TNFi-IR patients initiating treatment with TCZ + DMARD (TNFi-IR TCZ) or TNFi + DMARD (TNFi-IR TNFi). Patients initiating treatment with TCZ generally had more severe disease and longer disease duration compared with the corresponding TNFi group. Significantly more patients achieved remission (DAS28 ESR <2.6) in the TCZ groups compared with corresponding TNFi groups (DMARD-IR, TCZ 44.0 % vs. TNFi 29.6 %; monotherapy, TCZ 37.2 % vs. TNFi 30.2 %; TNF-IR, TCZ 41.3 % vs. TNFi 19.2 %; p < 0.001 for all comparisons). More patients achieved moderate–good responses (EULAR criteria) in the TCZ treatment groups (79–85 %) compared with TNFi treatment groups (65–81 %). Patient-reported outcomes showed greater improvements in TCZ compared with TNFi groups. In patients with inadequate response to DMARDs and/or TNFi treated in routine clinical practice, TCZ in combination with DMARDs or as monotherapy resulted in significantly more patients achieving remission and more marked improvements in patient-reported outcomes compared with TNF inhibitors.

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Background Certolizumab pegol (CZP) demonstrated a fast response and acceptable safety profile in clinical studies in rheumatoid arthritis (RA).1-3 Objectives To assess use of CZP in daily clinical practice in Germany. Methods The efficacy and tolerability of CZP (approved dosage: 400 mg at Weeks [Wks] 0, 2, and 4, then 200 mg every other Wk) is being assessed among 1068 patients (pts) with RA from 160 sites in the ongoing FαsT trial. Primary endpoint is DAS28(CRP) remission at Wk 104. At the cut-off date for this interim analysis (July 2011) 665 pts were enrolled. Wk 12 efficacy and safety data is reported in 160 pts with an available DAS28(CRP) value at baseline (BL) and Wk 12 (±1). Wk 52 (±8) efficacy is reported in 56 pts who completed up to 1 year and have non-missing observations (NMO). Results Of the 160 pts, 73% were female, mean age 54 years (yrs). At BL, 81% pts were RF positive and 79% ACPA positive. 50%/16% had received prior TNF inhibitors/other biologics, 90% had prior synthetic DMARDs. Mean RA duration was 10.7 yrs; mean CRP was 19.4 mg/L. Mean (SD) BL scores were: TJC 9.5 (6.8), SJC 7.6 (5.9), CDAI 29.9 (12.6), DAS28(CRP) 4.9 (1.0), DAS28(ESR) 5.4 (1.1) HAQ-DI 1.3 (0.7). Of the 160 pts, mean change from BL was -1.42 (1.3) in DAS28(CRP) at Wk 12 and 30.6%/16.3% were in DAS28(CRP) remission (REM)/low disease activity (LDA). Disposition of the 160 pts at Wk 52 is divided into pts with available DAS28(CRP) values (36.3%), pts who did not reach Wk 52 yet (38.3%) and pts who discontinued between Wk 12 and 52 (25%). 56 pts with NMO at Wk 52 reported mean (SD) changes from BL in DAS28(CRP) of -1.61 (1.1) at Wk 12 and -1.77 (1.3) at Wk 52. Of these 56 pts, at Wk 12 33.9%/28.6% and at Wk 52 44.6%/19.6% were in REM/LDA. The sum of the categories LDA/REM was similar (∼60%) at Wk 12 and 52 (Figure). Incidence rate (IR) of adverse events (AE) was 90 cases/100 pt-yrs (38 infections) and the IR of serious AE was 10.5 cases/100 pt-yrs. No deaths or cases of TB were reported. Conclusions In the FαsT non-interventional study, “real-life” RA pts treated with CZP achieved a fast reduction of disease activity by Wk12 which further improved for pts with available DAS28(CRP) values at Wk 52. Incidence and severity of AE was consistent with previous CZP experience and in line with the summary of product characteristics. References Arthritis Rheum 2008;58:3319–3329. Ann Rheum Dis 2009;68:797–804. Ann Rheum Dis 2009;68:805–811. Disclosure of Interest G. Burmester Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, U. Müller-Ladner Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, H. Nüsslein Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, U. von Hinuber Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, E. Edelmann Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, J. Detert Consultant for: UCB Pharma, M. Höhle: None Declared, C. Richter Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, T. Klopsch: None Declared, T. Kumke Employee of...